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Biomedical subjects

P G Gill

Publications and source records attributed to P G Gill.

At least 19 recordsLinked to original sources

Clinical and pathological factors predictive of lymph node status in women with screen-detected breast cancer.

Two thousand one hundred and thirty five asymptomatic invasive breast cancers detected through screening mammography were analysed to identify predictors of lymph node involvement. Multivariable analysis indicated that predictors included larger tumour diameter, an infiltrating ductal or lobular histological type, multifocal disease, a palpable lesion, and a younger age at diagnosis. An association also was found between nodal involvement and the presence of an extensive in situ component (EIC). Grade was associated with nodal involvement as a univariate predictor. It would be more accurate for screening assessment clinics to use models for predicting nodal status that were customised to their own experience rather than generic models developed in other settings that related predominantly to symptomatic cancer. These models could assist clinical decision-making on axillary node dissection and give guidance to pathologists on numbers of tissue sections to examine.

Adenocarcinoma↗

Detection by screening mammography is a powerful independent predictor of survival in women diagnosed with breast cancer.

Four hundred and sixteen invasive breast cancers, detected initially by mammography, were compared with 929 presenting symptomatically, all treated at a South Australian teaching hospital. Predictable differences included lower stages and grades, less vascular invasion and proliferative activity, and more hormone-receptor expression among the mammographically detected. Unpredicted differences included significantly higher survivals for mammographically detected cases throughout the 9 year follow-up period after adjusting for stage and the Nottingham Prognostic Index. In a multivariable analysis, differences in stage, grade, and hormone receptor expression accounted for only about half the survival advantage of mammographically detected tumours. Accounting for additional person and tumour characteristics had only a marginal effect on this result. This suggests that detection by mammography has independent favourable prognostic significance beyond that explained by conventional indicators. If confirmed, this finding would have important implications for the prognostic advice given to women and may merit further investigation into its underlying biological mechanisms.

Aged↗

Removal of two sentinel nodes accurately stages the axilla in breast cancer.

BACKGROUND: Assessment of lymph node status in breast cancer is still necessary for staging. Sentinel lymph node biopsy (SNB) may provide accurate staging with less morbidity than axillary clearance. The aim of this study was to assess the effect of the number of sentinel nodes removed on the false-negative rate. METHODS: Data were collected prospectively from 395 women undergoing SNB for breast cancer, between June 1995 and December 2001. All nodes that were hot and/or blue were removed and analysed. RESULTS: During this interval 136 patients who had SNB were lymph node positive. The median number of sentinel nodes removed was two (range one to five). The overall false-negative rate of SNB in these women was 7.1 per cent. If only one sentinel node had been removed, the false-negative rate would have been 16.5 per cent. The removal of more than two nodes had no effect on axillary staging in all but two women. CONCLUSION: In early breast cancer, when there were multiple sentinel nodes, removal of two sentinel nodes significantly reduced the false-negative rate compared with removal of one node. Removing more than two sentinel nodes did not significantly reduce the false-negative rate further.

Adult↗

Clinical impact of false-negative sentinel node biopsy in primary breast cancer.

BACKGROUND: The aim was to assess the false-negative sentinel node biopsy rate in women with early breast cancer and its implications in patient treatment. METHODS: Between January 1995 and March 2001, 328 consecutive patients with clinically lymph node-negative primary operable breast cancer underwent lymphatic mapping and sentinel node biopsy using a combination of preoperative lymphoscintigraphy and/or blue dye. All underwent immediate axillary dissection. The intraoperative success rate in sentinel node identification, false-negative rate, predictive value of negative sentinel node status and overall accuracy were assessed. The clinical features and primary tumour characteristics for each false-negative case were reviewed. RESULTS: The sentinel node was identified in 285 (86.9 per cent) of 328 women. The false-negative rate was 7.9 per cent (eight of 101). Most members of the breast multidisciplinary team would have instituted adjuvant systemic therapy for six false-negative cases based on clinical features and primary tumour histology. In all, only two (0.7 per cent) of 285 women who had sentinel node biopsy may have had their management and survival prospects potentially jeopardized owing to a false-negative sentinel node. CONCLUSION: The results of this study suggest that the clinical impact of a false-negative sentinel node is low.

Aged↗

Tumour location and prognostic characteristics as determinants of survival of women with invasive breast cancer: South Australian hospital-based cancer registries, 1987-1998.

Survivals from breast cancer varied by location of lesion (P<0.001), with 10-year survivals of 61% applying for central (n=772), 73% for medial (n=350), and 72% for lateral (n=966) lesions. Univariate analyses of determinants of central locations indicated that the following were predictive: a more advanced TNM stage (P<0.001); a larger tumour diameter (P=0.002); a higher grade (P=0.032); a negative oestrogen receptor status (P=0.004); a negative progesterone receptor status (P=0.004); and histological type (P=0.011), with more of the lobular lesions being located centrally. Cox proportional hazards regression indicated that the relative risk (95% confidence limits) of case fatality for central, as opposed to other, lesions reduced from 1.46 (1.20, 1.78) to 1.16 (0.95, 1.41) when stage was added to the model, with no other factor having an additional conditioning effect. It is concluded that central lesions have worse outcomes, mostly due to their more advanced stages. Means of finding these tumours earlier should be investigated.

Journal Article↗

Quality assurance in a multidisciplinary symptomatic breast assessment clinic.

BACKGROUND: Although quality assurance guidelines for surgeons have been issued and adopted for use in population-based breast screening programs in Australia, similar guidelines are unavailable for women referred with symptomatic breast problems. METHODS: Six hundred and ninety-six women who attended the Royal Adelaide Hospital Women's Health Centre between February and November 1998 for investigation and management of a new breast-related complaint were prospectively evaluated. Investigation strategies and outcomes of the initial consultation were determined and the results compared with the performance quality standards for symptomatic breast disease according to the British Association of Surgical Oncology (BASO) Breast Surgeons' Group. RESULTS: A breast lump was the presenting symptom in 45%, while breast pain was present in 26%. Ninety per cent of women referred with breast symptoms were given a definitive benign or malignant diagnosis at the initial clinic visit. Although the median time delay between the date of general practitioner referral and breast clinic appointments for all patients was < or =7 days, the time delay for 'urgent' cases was not met according to BASO performance indicators. All other Royal Adelaide Hospital Breast Clinic audit data were within the range suggested by BASO performance indicators for new consultations in a symptomatic breast assessment clinic. CONCLUSIONS: A multidisciplinary breast clinic in a public hospital setting is able to provide clinical services to symptomatic women, with the majority of patients obtaining a confident diagnosis at the first presentation. Performance indicators for symptomatic breast disease are useful in identifying inadequacies at the clerical or clinical level which, following the implementation of subsequent changes, may lead to improvement in patient outcomes.

Adolescent↗

Computer simulations of lymph node metastasis for optimizing the pathologic examination of sentinel lymph nodes in patients with breast carcinoma.

BACKGROUND: Many empiric protocols are used to detect metastases in sentinel lymph nodes (SLNs), but comparison of the efficacy of these methods is impractical because tissue is lost in processing, making reassessment with another policy difficult. Consequently, performance indicators of this test are largely unknown. DESIGN: The authors retrospectively examined 112 SLNs removed from 89 patients with breast carcinoma treated at the authors' institution and used the histologic data to devise a mathematic model of a SLN with Matlab modeling software. The authors simulated examination of this computer-generated (virtual) lymph node according to several macroscopic and histologic sampling protocols and for each protocol assessed the probability of detecting micrometastases of specified sizes. The authors used published costing figures to estimate the cost of the policies. RESULTS: Direct comparison of 6 sectioning strategies currently in use by pathology laboratories showed the chances of detecting a 500-microm metastasis ranged from 20% to 75%. Four of the 6 protocols had a less than 30% chance of detecting metastases of this size. The detection rate of smaller metastases was poorer. Cost was not a good discriminator because some policies were more efficient than others. CONCLUSIONS: The detection of metastases is highly dependent on the methods used to look for them. The authors' simulations suggest that commonly used methods of examining lymph nodes have high false-negative rates, particularly for small metastases. There is an urgent need for pathologists and clinicians to agree on the minimum size of SLN metastases that will be sought by histology and set standard methods for examining these lymph nodes.

Breast Neoplasms↗

Sentinel node biopsy in breast cancer: recommendations for surgeons, pathologists, nuclear physicians and radiologists in Australia and New Zealand.

BACKGROUND: Assessment of axillary lymph node status is necessary for patients with invasive breast cancer. Sentinel node biopsy is a new minimally invasive technique that may provide accurate assessment of regional lymph node status while limiting the morbidity associated with axillary clearance. METHODS: A workshop conducted in Adelaide in November 1998 aimed to assess current sentinel node mapping and biopsy techniques, and make recommendations regarding its application in the surgical management of early breast cancer in Australia and New Zealand. RESULTS: At the conclusion of the workshop, a consensus was reached regarding indications, exclusions, sentinel node mapping/biopsy technique, nuclear medicine requirements, pathology and safety of sentinel node biopsy in breast cancer. It was agreed that a feasibility study according to an agreed prospective protocol was necessary to validate the technique by breast surgeons. Surgeons that satisfied validation criteria for the feasibility study could then consider a prospective randomized study comparing sentinel node biopsy with standard axillary dissection. CONCLUSIONS: Sentinel node biopsy in breast cancer involves close cooperation between members of a multidisciplinary team including surgeons, nuclear physicians, pathologists and radiologists. Although the technique has the potential to reduce morbidity associated with axillary surgery, surgical performance in this area will need to be closely monitored to ensure that the technique does not fall into disrepute by adversely affecting breast cancer prognosis.

Australia↗

Clinical and histological factors associated with sentinel node identification in breast cancer.

BACKGROUND: Although sentinel lymph node biopsy is likely to be offered as a method of assessing nodal status in primary breast cancer, the inability to identify the sentinel node at the time of surgery will limit the number of patients who may benefit from the procedure. The purpose of the present study was to identify factors that are associated with intraoperative identification of the sentinel node(s). METHODS: Between September 1995 and May 1999, lymphatic mapping using a combination of preoperative lymphoscintigraphy and/or blue dye was performed on 169 consecutive patients with clinically lymph node-negative primary operable breast cancer. Clinical and histological factors were assessed using univariate and multivariate analysis to determine those that were associated with intraoperative identification of the sentinel node. RESULTS: The sentinel node was identified at the time of surgery in 142 cases (84%). Of the clinical factors assessed, preoperative identification of the sentinel node on lymphoscintigraphy (P < 0.0001), use of blue dye in combination with isotope (P = 0.001), symptomatic palpable tumours (P < 0.05) and the experience of the surgeon (P = 0.03) were significant in identifying the sentinel node at operation. No histological factor was associated with intraoperative identification of the sentinel node. Using multivariate analysis, positive identification of the sentinel node on lymphoscintigram, the experience of the surgeon and the use of both blue dye and isotope for sentinel node mapping were independent factors associated with intraoperative sentinel node identification. The lymphoscintigram result was the strongest independent factor according to its beta value, a measure of the weight of significance. CONCLUSION: Patients undergoing sentinel lymph node mapping and biopsy should be warned of the possibility of failure of sentinel node identification at operation. Our results suggest that the best predictor of intraoperative sentinel node identification is the visualization of the sentinel node on preoperative lymphoscintigraphy. The result of the lymhoscintigram may allow for additional preoperative counselling of the patient regarding the success or failure of sentinel node biopsy. Technical factors such as the experience and diligence of the surgeon, as well as the sentinel node mapping technique, are also important in determining the success of the procedure.

Adult↗

Reliability of sentinel node status in predicting axillary lymph node involvement in breast cancer.

OBJECTIVES: To assess the reliability of determining sentinel node status in staging regional lymph nodes in breast cancer. DESIGN AND SETTING: Prospective validation study in a major public teaching hospital, comparing histological sentinel node status with that of remaining axillary nodes. PATIENTS: 117 women who underwent sentinel node biopsy and axillary dissection for primary breast cancer between 1995 and 1998. MAIN OUTCOME MEASURES: Intraoperative success rate in sentinel node identification; false negative rate; predictive value of negative sentinel node status; overall accuracy of sentinel node status. RESULTS: The sentinel node was identified at operation in 95 patients (81.2%). Tumour involvement of the sentinel node was demonstrated in 29 of 31 women (93.5%; 95% CI, 79%-99%). Sixty-four of the 66 women in whom the sentinel node was negative for tumour showed no further involvement of remaining axillary nodes (standard haematoxylin-eosin histological assessment), giving a predictive value of negative sentinel node status of 97% (95% CI, 89%-100%). The overall accuracy in 95 women in whom sentinel node status was compared with axillary node status was 97.9%. CONCLUSIONS: Histopathological examination of the sentinel node is an accurate method of assessing axillary lymph node status in primary breast cancer and is likely to be incorporated into future surgical management of women with primary breast cancer.

Antimony↗

Lymphoid cell infiltration during breast cancer growth: a syngeneic rat model.

The systematic study of potential alterations in lymphoid infiltrates during tumour growth is extremely limited in humans. Therefore, development of a model utilizing a spontaneously arising mammary adenocarcinoma in Dark Agouti rats was adopted for the study of the dynamics of lymphoid cell infiltration during tumour development. Syngeneic rats were inoculated with tumour cell suspensions and the tumours were resected from 5 to 15 days. Serial sections were immunohistochemically stained using a panel of monoclonal antibodies. Irrespective of tumour age, ED2 (macrophages) and W3/25 (CD4)-positive cells were the most prominent cell infiltrates in tumours. There were no significant differences in cell counts for any marker between 8-day and 15-day tumours. However, in 5-day tumours there were significantly fewer macrophages, OX19+ T cells, W3/25+ cells, OX8+ (CD8) cells and OX62+ dendritic cells. Interleukin-2 receptor alpha chain expression was low at all examined stages of tumour growth, indicating a lack of tumour infiltrating lymphocyte (TIL) activation and/or possible TIL anergy. B cell staining was absent in all tumours, negating the possibility of these cells mediating coregulatory signals for TIL activation in the micro-environment of established tumours. The results parallel previous immunohistochemical findings in humans, suggesting that a dysfunctional local immune response in breast cancer may be determined very early during tumour development.

Adenocarcinoma↗

The utility of the proliferative index in pretreatment biopsy specimens of esophageal squamous cell carcinoma.

The proliferative index detected immunohistochemically by monoclonal antibody MIB-1 from pre-treatment biopsy tissues of 33 patients with esophageal squamous cell carcinoma who underwent preoperative concurrent chemoradiotherapy was evaluated in relation to clinicopathologic features and chemoradiotherapeutic responses. The response to chemoradiotherapy was assessed both endoscopically and pathologically and classified as complete or partial response. Higher MIB-1 LI was significantly associated with lymph node metastases, suggesting that detection of MIB-1 LI from biopsy tissues may contribute to pre-treatment staging of tumors and prediction of persistence of lymph node involvement after chemoradiotherapy, which would permit the optimization of systemic treatment for individual patients. Statistically, significant correlation existed between higher MIB 1-LI and poor overall survival, implicating the prognostic significance of the MIB-1 LI in patients undergoing multimodality treatment. No significant relationship was found between the MIB-1 LI and either endoscopic or pathologic responses, although a trend for tumors with lower MIB-1 LI to have better responses was observed.

Adult↗

Clinical and radiological predictors of complete excision in breast-conserving surgery for primary breast cancer.

BACKGROUND: Local recurrence after conservative surgery for breast cancer usually results from growth of residual cancer adjacent to the excised primary tumour or from multicentric disease. Complete local excision (CLE) confirmed histologically is essential to ensure that the risk of local recurrence is minimal. This study was undertaken to determine that clinical or radiological factors may assist the surgeon at the time of surgery to achieve this aim. METHODS: A retrospective review of 101 cases treated by conservative surgery identified 70 cases of CLE and 31 of incomplete local excision (ILE). Clinical, surgical and histopathological data were taken from hospital records. Mammographic features and those of specimen X-rays were evaluated without knowledge of the histopathological outcome of surgery. RESULTS: Complete excision was significantly associated with type of operation (lumpectomy vs wide local excision/quadrantectomy, P < 0.003), absence of calcification (P < 0.03) and the presence of a mass on mammography (P = 0.05). Tumour size (> 2.5 cm) and the presence of extensive ductal carcinoma in situ (DCIS) were associated with incomplete excision (P = 0.0005). No relationship was demonstrated with patient age, breast size, breast density, tumour grade, receptor status, axillary nodal status or spicules on X-ray and completeness of excision. Specimen X-ray had a positive predictive value of 94% with CLE. CONCLUSIONS: Clinical and pre-operative mammographic parameters are important for predicting CLE for breast cancers treated by breast-conserving surgery. Specimen radiology for palpable lesions can confirm excision of the cancer and permit re-excision of breast tissue at the time of initial surgery. Its role in determining CLE should be further evaluated.

Adult↗

Laparoscopic versus open splenectomy for immune thrombocytopenic purpura.

BACKGROUND: We sought to determine whether laparoscopic techniques can reduce the operative morbidity of surgery in patients undergoing splenectomy for immune thrombocytopenic purpura (ITP). METHODS: All patients (60) undergoing splenectomy for ITP at the Royal Adelaide Hospital from January 1985 to November 1995 were reviewed. Results of patients undergoing open operation were obtained by means of retrospective case note review, whereas details of all patients undergoing laparoscopic splenectomy were collected prospectively and maintained on a computerized database. RESULTS: Forty-seven patients underwent splenectomy with an open technique and 13 with a laparoscopic technique. Patient groups were demographically similar. All laparoscopic procedures were completed with the laparoscopic technique. An accessory spleen was also removed at laparoscopic operation from two (15%) patients and at open operation from three patients (6%). Two more accessory spleens were missed at the original procedure, one at open operation and one at laparoscopic operation. These required later removal by using open and laparoscopic techniques, respectively. Blood and platelet transfusion requirements were reduced by the laparoscopic approach. Although mean operating times were similar (87 versus 88 minutes), laparoscopic splenectomy was associated with a greatly reduced postoperative hospital stay (10 versus 2 days, median; p < 0.0001) and no major morbidity. Long-term normalization of platelet counts was similar for the two techniques. The laparoscopic approach resulted in a reduction in hospital treatment costs from $4224 to $2238 per case (cost savings of $1986 per case). CONCLUSIONS: Laparoscopic splenectomy results in improved clinical outcomes and reduced costs for patients undergoing elective splenectomy for ITP.

Adolescent↗

A combined modality approach to the management of oesophageal cancer.

This study aims to update the experience of multimodality approaches in the management of oesophageal cancer that have been adopted in several Australian and New Zealand hospitals. Between 1984 and 1985, 92 patients received pre-operative radiotherapy (30-36 Gy over 3 weeks) and one of two chemotherapy regimes (one or two courses of i.v. cisplatin 80 mg/m2 plus a 4-5 day continuous i.v. of fluorouracil 5-800 mg/m2/day) concurrently prior to surgery. Eighty-two patients (89%) underwent resection as planned. Operative specimens were microscopically free of residual tumour in 18 patients. Eight patients (9%) had treatment-related deaths: seven from surgery and one due to pre-operative chemoradiation. The Kaplan-Meier 5-year cause-specific survival estimates were 32.9 +/- 7.8% for the 58 patients with squamous cancer and 0% for the 32 with adenocarcinoma. Complete pathological response to the pre-operative regime was more common in females and was associated with a survival advantage. Five-year cause-specific survival expectation in patients who experienced a complete pathological response was 71.5 +/- 12.4%, whereas it was only 15.9 +/- 5.6% in patients who had residual cancer in their surgical specimens. Although less toxic the pre-operative regime utilizing only one cycle of chemotherapy was no less efficacious either in producing a complete pathological response or in terms of survival expectation. This uncontrolled pilot study has produced encouraging long-term results, especially for patients with squamous carcinoma that experienced a complete response to pre-operative synchronous chemoradiotherapy. A randomized controlled study comparing surgery alone with (one cycle) chemoradiation followed by surgery is now underway.

Adult↗

Medroxyprogesterone acetate addition or substitution for tamoxifen in advanced tamoxifen-resistant breast cancer: a phase III randomized trial. Australian-New Zealand Breast Cancer Trials Group.

PURPOSE: To determine whether a strategy of adding medroxyprogesterone acetate (MPA) to tamoxifen (TAM) is superior to the substitution of MPA for TAM among women with advanced breast cancer and disease progressing on TAM. To assess the patterns or response and subsequent progression in sites and tissues according to prior involvement and treatment. PATIENTS AND METHODS: Two-hundred-fifteen postmenopausal women with advanced breast cancer progressing on TAM after receiving TAM for at least six months were randomized: 109 to add MPA 500 mg/day orally (TAM + MPA), and 106 to stop TAM and to substitute MPA. RESULTS: There were no significant differences between the groups with respect to complete plus partial response rates: TAM + MPA 10%, MPA 9%, median time to progression TAM + MPA 3.0 months, MPA 4.5 months, or median overall survival, TAM + MPA 17.2 months, MPA 18.4 months. In a multivariate model, prognostic factors significant for a shorter time to disease progression were worse for performance status, involvement of more than one tissue, prior radiotherapy, and shorter time from recurrence after primary therapy to randomization. Adjusting for these factors, treatment with TAM + MPA was associated with a higher relative risk for disease progression, with a hazards ratio of 1.31, but this was not significant (95% confidence interval, 0.98 to 1.74; P = .067). However, in an exploratory analysis, the time to disease progression, among patients with progesterone receptor positive (PR+) tumors, was 6.3 months with MPA versus 2.9 months with TAM + MPA, with a hazards ratio of 1.92 (95% confidence interval, 1.12 to 3.32; P = .02). There was a significant interaction, P = .04, between PR status and treatment, indicating an advantage to treatment substitution for those who have PR+ tumors. Tumor response occurred in 14% of assessed metastatic sites. Subsequent progression occurred in a new tissue alone in 13% of patients, in both new and previously involved (old) tissues in 76%, and in old tissues only in 11%. In 23% of patients, progression occurred only at a new site, in 50% at both old and new sites, and in 27% only at old sites. No significant differences in the patterns of response or progression were seen in the different treatment groups. CONCLUSION: Among women with breast cancer whose disease is progressing after at least six months of treatment with TAM, there is no advantage to maintaining TAM when MPA is to be given. An overall effect of treatment on the pattern of failure at old sites or at new sites or tissues cannot be discerned.

Aged↗